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significantly reduced serum cholesterol, low-density lipoprotein cholesterol (LDLC) and apolipoprotein B levels in post-menopausal women. In premenopausal women, the effects on lipids and lipoproteins was smaller with a significant fall in total serum cholesterol and LDLC only. The trial has approval to accrue up to 1000 women.

90286806 High-density llpuproteln cholesterol and coronary artery diseaw Survey of the evidence Rilkind B.M. Lipid Metabolism-Atherogenesis Branch, Division of Heart and Vascular Diseases. National Heart, Lung. and Blood Institute, Bethesda. MD 20892 AM. J. CARDIOL. 1990 66/6 (3AdA)

The epidemiologic evidence linking high-density lipoprotein (HDL) levels with coronary artery disease (CAD) is persuasive. Case-control studies have shown CAD patients to have lower HDL levels than con- trol subjects. Several large-scale, observational epidemiologic studies in the United States and abroad have shown a strong independent inverse relation between HDL and CAD. Women have a lower incidence of CAD than men of the same age; this has been attributed to their higher HDL levels. Postmenopausal women taking estrogen replacement therapy have higher HDL and lower low-density protein (LDL) levels, and a much lower incidence of CAD. Statistical analysis suggests that much of this is attributable to HDL levels. In several clinical trials, reduced levels of total or LDL cholesterol have been accompanied by in- creased HDL levels. Cox proportional hazards analysis suggests that the increment in HDL levels made an independent contribution to the reduction in CAD risk. In several angiographic studies, the increase in HDL may have contributed to the decreased progression, increased stabilization and possible regres- sion of coronary lesions. Despite this range of impressive evidence, a number of unresolved issues have prevented the emergence of a consensus regarding the prevention of CAD by increasing HDL levels. Between- population comparisons of HDL and CAD do not match the within-population relations. Animal research on the relation between HDL, atherogenesis and CAD has been relatively scanty. Although much evidence suggests that reverse cholesterol transport partially explains the protective effect of HDL, there are still doubts as to its role. Problems with measurement of HDL have inhibited widespread recommendations for its use in prevention programs. Our ability to increase low HDL levels by hygienic means is uncertain, and there is insufficient information regarding the use of drugs for such a purpose. The recent report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, while not advocating universal screening for HDL, did assign a risk- factor status to a low HDL level, and recommended HDL measurement in a large proportion of persons classified initially on the basis of total cholesterol levels. The results of the Helsinki Heart Study support the use of gemfibrozil in patients with high-risk LDL levels who also have borderline hypertriglyceridemia and low HDL levels.

90291970 The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women Mortola J.F.; Yen S.S.C. Department of Reproductive Medicine, University of Calijornia. 225 Dickinson Street, San Diego, CA 92103-1990 J. CLIN. ENDOCRINOL. METAB. 1990 71/3 (696704)

To discern the pharmacological effects of dehydroepiandrosterone (DHEA) in older women with low en- dogenous DHEA and DHEA sulfate (DS), 1600 mg/day (in four divided doses) were administered orally to six postmenopausal women for 28 days in a double blind placebo-controlled cross-over study. Serum concentrations of androgens after the first 400-mg dose of DHEA increased rapidly and reached a max- imum at 180-240 min, resulting in increases over baseline of 6-fold for DHEA (5.8 f 2. I to 28.8 ?? 5.5 nmol/L), IZfold for DS (3.0 t I .6 to 28.2 f 4.6 [ 225) (230) [ 225 )mol/L) and androstenedione (I .4 f

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0.3 to 19.5 * 9.8 nmol/L), 2.5-fold for testosterone (0.7 f 0.1 to 2.2 * 0.6 nmol/L), and IS-fold for dihydrotestosterone (0.2 f 0.06 to 2.73 f 1.0 nmol/L), but estrone, estradiol, and sex hormone-binding globulin (SHBF) were unchanged. Assessment at weekly intervals revealed a further increase in all an- drogens which was maximal at 2 weeks and remained markedly elevated, although it declined somewhat by 4 weeks. The increments observed after 2 weeks of DHEA administration reached I S-fold for DHEA (71.9 ?? 14.2 nmol/L), 9-fold for testosterone (6.5 f 1.7 nmol/L), and 20-fold for DS (65.1 f 14.9 nmol/L). androstenedione (30.5 ?? 11.5 nmol/L), and dihydrotestosterone (3.8 f 1.5 nmol/L). Both estrone and estradiol showed a progressive increase to 2-fold the basal value at 4 weeks. Integrated SHBG and thyroid binding globulin levels decreased (P&h; 0.05) during DHEA treatment. However, LH, FSH. body weight. and percent bvody fat, as measured by underwater weighing, were unaltered during the 4-week experi- ment. A marked decline of 11.3% (P &It; 0.05) in serum cholesterol and 20.0% (P &It; 0.05) in high density lipoprotein noted within the first week of DHEA administration persisted for the 28-day period and was accompanied by a nonsignificant downward trend in low density lipoprotein, very low density lipopro- tein, and triglycerides. Peak insulin levels during the 3-h oral glucose tolerance test were significantly higher (P &It; 0.05) after the 289 days of DHEA (I 126 f 165 vs. 746 * 165 pmol/L) and were accompanied by a 50% increase in the integrated insulin response (P &It; 0.01) without a significant change in fasting glucose insulin or glucose-6-phosphate dehydrogenase values. These data show that oral DHEA is rapidly absorbed, and a prompt conversion to DS as well as all potent androgens and estrogens occurs with a sustained effect for the 28-day duration of treatment. Thus, in postmenopausal women there appears to be abundant and effective enzymatic systems for the biotransformation of DHEA to C-19 and C-18 sex steroids. Further, pharmacologically imposed DHEA in postmenopausal women induced insulin resistance, altered cholesterol and the high to low density lipoprotein ratio, and decreased circulating SHBG and thyroid binding globulin concentrations. Our findings, which contrast sharply with those of a previous experiment in young men, appear to result from the induction of a highly androgenic state and its impact on several endocrine-metabolic parameters in older postmenopausal women.

90293545 Effect on bone of surgical menopause and estrogen therapy with or without progesterone replacement in cynomolgus monkeys Jayo M.J.; Weaver D.S.; Adams M.R.; Rankin SE. Department of Comparative Medicine, Bowman Gray School of Medicine, 300 South Hawthorne Road, Winston- Salem, NC 27103 AM. J. OBSTET. GYNECOL. 1990 163/2 (614-618)

The influence of estrogen replacement therapy on bone loss of surgically postmenopausal cynomolgus maca- ques was evaluated histomorphometrically using the first (L-l) lumbar vertebra and ex vivo dual photon absorptiometry of the third (L-3) lumbar vertebra. The animals were a subgroup of a larger study on the effects of estrogen replacement therapy on diet-induced coronary artery atherosclerosis. The three experimen- tal conditions were as follows: untreated females with oophorectomy, females with oophorectomy treated with continuous estrogen replacement therapy plus cyclic progesterone, and females with oophorectomy treated with estrogen replacement therapy. Bone mineral density (grams per square centimeter) of L-3. when covaried for body mass index (body mass index, body weight/(trunk length/100)2), was significantly lower for the oophorectomy group compared with the group treated by estrogen replacement therapy plus progesterone and estrogen replacement therapy groups (p = 0.018). When covaried for body mass index, trabecular bone volume percentage of a midsaggital section of L-l was not significantly different between groups, but the adjusted mean was greatest in the estrogen replacement therapy plus progesterone group, followed closely by the estrogen replacement therapy group, and was least in the oophorectomy group. When covaried for body mass index, trabecular plate number was significantly lower (p = 0.022) and mean trabecular plate separation was significantly higher (p = 0.033) in the oophorectomy group. Thus both estrogen replacement therapy and estrogen replacement therapy plus progesterone provided overall pro- tection against surgical menopause-associated bone mass loss. Cynomolgus macaques are an extremely useful animal model for estrogen replacement therapy use in prevention of postmenopausal bone loss.